The $1.55 million MIRA grant will enable Kekenes-Huskey and his team of researchers to develop large-scale, computer-based models to study the role of calcium regulation at a subcellular level. The role of calcium in the body is paramount, as its mismanagement is correlated with diseases including heart failure, Alzheimer’s disease and cancer.

“The focal point of our research is to work across disciplines to find new insights into how calcium signaling is modulated at the subcellular level, and thereby prioritize novel strategies to combat chronic diseases much faster,” Kekenes-Huskey said.

Research on calcium regulation in cells is predominantly conducted through experiments on living tissue. However, many questions about calcium mismanagement in disease are difficult or expensive to probe using conventional experimental techniques.

“There are a host of unintended consequences when probing living cells. Transgenic animals, for instance, often present changes in multiple signaling pathways relative to controls, which makes interpretation more challenging,” Kekenes-Huskey said. “Computational approaches allow scientists to toggle the expression of a single protein in a pathway, as an example, and monitor how the cellular phenotype is changed.”

Kekenes-Huskey takes a nontraditional approach in his research. He collaborates with experimentalists across scientific disciplines, including biochemistry, bioengineering and physiology, to create multiscale simulations of subcellular signaling. He began developing these computational models during his postdoctoral fellowship at the University of California San Diego with professors Andrew McCammon and Andrew McCulloch, where he focused on developing multiscale tools for cardiac modeling.

“Professor Kekenes-Huskey exemplifies what we are accomplishing at the University of Kentucky,” said Professor Mark Meier, chair of the chemistry department. “His interdisciplinary approaches using computational models are strengthening the scientific community’s ability to probe important questions relating to health and disease.”

MIRA is an experiment in funding science by supporting an investigator’s overall program of research through a single unified grant rather than providing individual project grant support. This funding experiment aims to increase investigators’ funding stability with the freedom to take on ambitious challenges and approach problems creatively.

According to NIGMS Director Jon R. Lorsch, “The overall goal (of the NIGMS MIRA) is to increase scientific productivity and improve the chances for important breakthroughs, in part by distributing funding more widely among the nation’s highly talented and promising investigators.”

NIGMS supports basic research that increases understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment and prevention. NIGMS-funded scientists investigate how living systems work at a range of levels, from molecules and cells to tissues, whole organisms and populations.